ChlamyChem is a collection of small molecules screened on Chlamydomonas reinhardtii. We performed a large scale high-throughput fitness screen on Chlamydomonas in triplicate and performed short term exposure assays to identify motility/phototaxis and photosynthesis modulators.

Abstract

Small molecules are valuable tools for understanding biological process and for treating human disease. Chemical biology, the interfacial discipline of using small molecules as probes to investigate biology, has been aided by the convergence of several advances including, the availability of large screening collections, the introduction of screening platforms in academic research and the use of model organisms to combine chemical and genetic perturbations. This approach can, provided the targets or target pathways are conserved, be applied across organisms, and their effects are typically rapid and reversible. Large-scale chemical biology screens have been pioneered with yeast, zebrafish, worms and cultured cells, and here we apply this approach to the green alga Chlamydomonas reinhardtii. This single-celled biflagellate alga is an excellent model to understand plant and animal biology and is well suited for small molecule studies because of its rapid growth and simple husbandry. Here we report on the results of an automated fitness screen of 5445 small molecules and we determined if these bioactives were cytocidal or cytostatic. In parallel to the fitness screens we performed a motility/phototaxis and photosynthesis assay. Cheminformatic analysis of these screens was used to construct a Naïve Bayes model that successfully predicts algal bioactive compounds. Additional analysis was used to cluster the data based on compound structure and activity revealing active core structures on Chlamydomonas. This resource of compounds and their phenotypic effects is available for individual queries and bulk download (Link).